Work has been undertaken to investigate the role of tetrahydrobiopterin (THB) in the synthesis of specific neurotransmitter substances. THB is the specific electron donor for several aromatic amino acid hydroxylases and is key for the synthesis of biogenic amines. An important aspect of our work during the past year has been an attempt to find an inhibitor of the synthesis of THB. Studies with PC12 cells suggest that N-acetyl serotonin may slow the synthesis of this important compound. Preliminary studies, however, indicate that while the levels of THB may be reduced in cells treated with N-acetyl serotonin little change occurs in the synthesis of catecholamines within these cells. In previous years we had attempted to examine the effect of administration of THB to man to determine whether it would enhance biogenic amine synthesis and whether such enhancement would be of benefit in diseases such as Parkinson's disease, dystonia, and endogenous depression. It would appear that the neurological symptoms in certain patients with dystonia are significantly improved by treatment with THB. Little clinical response was seen in Parkinson's disease or endogenous depression. However, the poor clinical response may be due to the fact that THB appeared to penetrate the blood brain barrier very poorly.